title: The importance of interaction with membrane lipids through the pleckstrin homology domain of the guanine nucleotide exchange factor for rho family small guanosine triphosphatase, FLJ00018.
abstract: FLJ00018, a heterotrimeric guanosine 5'-triphosphate (GTP)-binding protein (G protein) Gβγ subunit-activated guanine nucleotide exchange factor for Rho family small GTPases, regulates cellular responses, including cell morphological changes and gene transcriptional regulation, and targets the cellular membranes. FLJ00018 contains a Dbl homology (DH) domain in addition to a pleckstrin homology (PH) domain. Here we show that the PH domain of FLJ00018 is required for FLJ00018-induced, serum response element-dependent gene transcription. Although the PH domain of KIAA1415/P-Rex1, another Gβγ subunit-activated guanine nucleotide exchange factor for Rho family small GTPases, binds to phosphatidylinositol 3,4,5-triphosphate and phosphatidylinositol 3,4-bisphosphate, the PH domain of FLJ00018 binds to polyphosphoinositides including phosphatidylinositol 4,5-bisphosphate, and phosphatidic acid. These results suggest that FLJ00018 is targeted via its PH domain to cellular membranes.
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501–1193, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kimura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sato
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008563:Membrane Lipids / Q000378:metabolism*; D010957:Plasmids; D011485:Protein Binding; D064067:Rho Guanine Nucleotide Exchange Factors; D027602:Serum Response Element / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D020662:Guanine Nucleotide Exchange Factors; D008563:Membrane Lipids; C527535:PLEKHG2 protein, human; C453280:PREX1 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; D008156:Luciferases